AR’ Management of Infants of Diabetic Mothers Leandro Cordero, MD; Sergio H. Treuer, MD; Mark B. Landon, MD; Steven G. Gabbe, MD Objective: To describe the clinical outcome of infants born to mothers with gestational diabetes mellitus (GDM) and preexisting insulin-dependent diabetes mellitus (IDDM), Settings A tertiary care regional perinatal center with a specialized diabetes-in-pregnancy program, Design: Case series Results: Five hundred thiry infants were born to332.wor- ‘en with GDMand 177 women with IDDM. Thirty-six per ‘cent of these 530 newborns were large for gestational age, 02%6 were appropriate for gestational age, and only 2% were ‘small for gestational age. Seventy-six (14%) of all infants were born before 34 weeks gestation, 115 (22%) between 34and 37 weeks of gestation, and 339 (64%) at term. Two hundred thirty-three infants (479%) were admitted to the ‘neonatal intensive care unit due to respiratory distress syn- ‘drome (RDS), prematurity, hypoglycemia, orcongenital mal- formation. Hypoglycemia (more common among infants ‘ofmaternal diabetic classes C through D-R) was documented in 137 27%) ofall newborns. One hundred eighty-1o in- fants (34%) had RDS of varying severity. Polyeythemia (5% ofinfants), hyperbilirubinemia (25%) and hypocalcemia (496) were other morbidities present. Two hundred forty- fourinfantswereadmitted for routine careand enteral feed ings. Forty-three of these newborns required subsequent transfer o the neonatal intensive care unit for treatment of hypoglycemia (16 cases), RDS (19 cases), orboth (Beases). Roultine care failures were more common among infants whose mothers had advanced diabetes, but less frequent among breast-fed infants Conclusions: With modern management, fewer morbid des ean be expected in infants of diabetic mothers. Those infants born to women with IDDM remain at risk for hy- poglycemia, which can be treated in one half of the cases by enteral feedings alone. The majority ofcases of RDS are mild and require short admissions to special care nurser- {es, Optimal care of infants of diabetic mothersis based on prevention, early recognition, and treatment of common conditions, Severe congenital malformations, significant pre- maturity, RDS, recurrenthypoglycemic episodes, and asymp- tomatic infants of women with advanced IDDM should be admitted to special care nurseries, Breast-feeding among women with GDM and IDDM should be encouraged. Arch Pediatr Adolesc Med. 1998;152:249-254 NCREASED AWARENESS screening, ‘and identification have led to « _greater number of successful prey nancies among women with ges- tational diabetes mellitus (GDM) early recognition combined with treat- ‘ment of these complications, For example, rnconatal hypoglycemia, known to affect 5% to 30% of infants of diabetic mothers, ean be avoided in some cases by early breast- From the Departments of Pediatrics and Obstetrics (Dr Cordero) and Obsterics and Gynecology (Dr Landon), The Ohio State University ‘Medical Center, Columbus; Department of Pediatrics, University of Concepcion, ‘Concepcion, Chile (Dr Trewer «and Department of Obstetris and Gynecology, University of Washington, Seattle (Or Gabbe) and preexisting insulin-dependent diabe- tes mellitus (IDDM). It has been esti- ‘mated that more than 100000 infants of, diabetic mothers are born every year in the United States, Although perinatal mortal- ity among this group has declined," ex- cess neonatal morbidity remains a signi cant challenge.>° Suboptimal prenatal care along with poor maternal glycemic con- trol, vasculopathy, infection, and preg- nnancy-induced hypertension are factors as- sociated with poor perinatal outcome." Congenital malformations,”"® macroso- mia," respiratory distress syndrome (RDS),!* hypoglycemia," hyperbill- rubinemia" and hypocalcemia'” are some of the conditions most frequently diag- nosed in the ollspring of diabetic women. Successful management of infants of diabetic mothers is based on prevention oF feedings or formula-feedings and/orby in- ravenous dextrose administration." Comprehensive careof pregnant wom- cnwith diabetes mellitus hasbeen extensively described, * yet guidelines regarding the care of the infant are less well established. The purpose ofthis investigation was o charac- {erize the clinical outcome foralargecohort oftnfants ofdiahetic mothers delivered dur- {nga 3-year period, and to examine the ef- ficacy of our institutional diagnostic and therapeutic approach to their care es Between January 1, 1904, and December 31 1999, 509 women with diabetes mellitus were delivered of 491 singletons, 15 sets of twins, and 3 sets of tiplets. Three hun- dred ninety-four (77%) of the women were (©1908 American Med jamanetwork.com/ on 03/26/2019 Association, All rights reserved.PATIENTS AND METHODS The study population consists of mothers and their in- fantsborm at The Ohi late University Hosptial from 1994 through 1990, Demographic nd clinical characterise were obtained from our database and medical records. Clasfcation, diagnosis treatment, and cae of preg nant women with diabetes melitsin our institution based on specific recommendations Fetal assesment for insulin dependent women consists of twice-weekly nonsires test ing ginning a 32 weeks, unless othe isk lacors are pres ent” Women with diet-contolled GDM (cas A) undergo fonstres testing for spect sk actos or when they reach $o weeks, Women with insuln-requiring GDM (class A2) ae managed similar lo women who have preexisting di betes without vascular disease ‘Ourinsiational genes etablish that infants of da- besic mothers delivered before 34 weeks gestation and tose ‘vith significant major malformations or respitatory di tress, regal of gestational age, be admited diet tothe ‘sonata ntensiveeareun (NICU) from the delivery rom, Allnewborns admitted tthe NICU are prescribed 10% dex- trose in water, mL/kg per day ntravenowly thr bith ‘weight ic more than 1000 g, and 5% desiose in water, 100 InLlig per day, i less that 1000. Asympomati infants twhose mothers have preexisting diabetes also receive intr ‘enous dextrose supplementation inthe NICU a hoe born {oom with GDM who do at llintotheaove-deseibed Categoresareadmted tthe wel-baby nurseries forrouine Cateand breatorformafeedng Infantswho develop com- Plations that prompreubsequentadmision othe NICU are Conldred routine cae fares reas edingtstatlshory sierdelivery, but iberal formula supplementation isin ef fetioproentypepeemc eps fied into nonspecific mild or nonspecific moderate (lin cal signs and/or supplemental oxjgen requiements lst ing less than 6 or fees than 48 hours, respectively, and hyaline membrane disease, ranstent tachypnes, and persistent pulmonary hypertension ofthe newborn were Aiggnosed by clinical and radiologtcal signs Blood glucose sctecning was performed with chromogen reagent stripe (Accuchek advantages, Boerhinger Manthey, Indlanapo- iss Ind) read bya reflectance meter (AccuDala GTS, Deer hinger Mannheim), and true serum ghicose was measured bythe standard glucose oxidase method. Hypoglycemia was defined as ld ifthe te serum ghicose concentration was 1:7 to.22 mmol. G0-39 mg), moderate i 1 to Le mmol. 20-20 mgd), and severe ess than 1.1 mmol (220 mpl). Glucose was administered orally or intrave= Dowel slow infusion of 10% destose in water, Lk, followed by 10 ml/kg per day)" toallinfnts with or ith out symptoms provided that serum glace concentration decreased to les than 2.2 mmoV (<40 mg/dl) Poycy- thin was defined sa peripheral venous hematocrit greater than 0.65, and hyperblirubinera was defined ae i fect bilirubin serum level greater than 208 mol (12 mg/ A) and/orany hypeblrubinemiaequiting treatment (pho- totherapy). Hypoalcenia was defined by total seu alia talus lower than 1.30 mmol. (6 mg.) or tonized cal ‘ium levels below 100 mmol. (2 mba). atienswere cased int largeforgesationalage(LGA), appropriate forgestatlonalage (AGA) ars for gestational 4g¢ (SGA), according to the relationship between itrauter- itegrowih and gestational age” Proporonaevsdspropor- {Note grovah wss determined by ponderalindex.* infants ‘shove inh weight wasat least 4000 greqardes ofgesaional ‘ge were defined as macrosomi. "The Student test for independent samples was used to compare continuous variables, The y= tex was used to teat diferences in all categorical variables, The Mann- Whitney U test was used to compare noncaegorical va ales. Forward stepwiselogisti regression was sed to eva de the contribution of maternal diabetes class, gestational age, bh weigh, sex, mode of delivery. Apgar cores, mac: Tosomia, bresteeding, LGA, and SGA (lependent va thes) inthe prediction of routine care failure (indepen- dent variable) all statistical tests were led anda P value less than 05 was considered significant white, 07 (19%) were black, and the remaining 18 (3%) cither Asian oF Hispanic, Maternal age ranged from 16 to 44 years, with 302 (77%) of the mothers in the 20- to 36- year age group. Approximately one third ofall mothers were primigravidas, Further clinical and demographic informs- tion for the study population is presented in Table 1 Two hundred thirty-three (45%) ofthe mothers were classified as diabetes class A1, while 99 (19%) were women ‘with GDM who required insulin for control (class A2). Sixty ‘ight mothers (13%) were class B, 60 (12%) were class C, and 49 were (10%) class D-R. In our institution, the over all cesarean section rate is 21% for nondiabetics and 44% for diabetics (29% for class A1, 49% for class A2, and 60% for classes B through D-R), Newborn birth weight ranged [rom 700 10 5400 g and ‘gestational age ranged from 28 to 42 weeks (mean values, 3154 gand 36.8 weeks, respectively). Three hundeed thirty nine (64%) of all infants were born at term, and 7 (14%) ‘were born before 34 weeks gestation (Table 1). Amongall, deliveries in our institution, the corresponding rates are 74% and 14%, respectively. The percentage of infants born at or before 33 weeks of gestation was similar among the dif ferent classes of diabetes. Information regarding breast-feeding was available from the medical records f 356 infants, One hundred thirty two (37%) were either partially or exclusively breast-fed. Breast-feeding was more common among infants of moth- ers with class Al diabetes (43%) than among those born to mothers with class D-R diabetes (22%). There were 4 neonatal deaths among the 530 in- fants: a septic premature infant born at 28 weeks’ gesta- tion, an infant with diaphragmatic hernia, another with ring Y chromosome, and one with transposition of the great vessels who died following operation. NICU ADMISSIONS Two hundred forty-seven (47%) ofall infants required ad- mission to the NICU (Figure). The number of patients ranged from 36% forclass Al 19 68% for class D-R. Included were 7o infants whose gestational age was 33 weeks or les, 22 infants with congenital malformations, 10 patients with (©1908 American Med jamanetwork.com/ on 03/26/2019 Association, All rights reserved."O'S indcates cesarean section: G4 gestatonal age, LGA lage fr gsttonal age: AGA appropri for gesttonal age: and SGA smal fo gestibonal age miscellancous conditions (apnea, cardiac arrhythmias, poor feeding, neonatal depression), and 103 infants with gesta- tional age of 34 weeks or more with RDS. Hypoglycemia ‘was the only admission diagnosis in 32 infants. RESPIRATORY DISTRESS. ‘One hundred cighty-two (34%) of the 530 infants pre- sented with RDS of varying severity (Rabble 2). Respirs- tory distress syndrome, by maternal diabetes class tion, was present in 25% of Al, 38% of A2, 35% of B, 47% of C, and 56% of D-R. Of all infants with RDS, 84 (40%) had nonspecific mild RDS, 41 (23%) had nonspecific mod- ‘erate RDS, and 13 (7%) had transient tachypnea. All these 3 forms of delayed transition combined accounted for 76% ofall the RDS cases, Hyaline membrane disease was found in 34 (6%) ofthe infants and persistent pulmonary hyper- tension was found in 10 (2%). Sixty-five (36%) of the 182 infants with RDS were treated with mechanical ventila- tion, All infants with hyaline membrane disease received ‘exogenous surfactant (beractant [Survantal). CONGENITAL MALFORMATIONS. ‘Twenty-six (59%) of the 530 infants presented with con- {genital malformations, and 22 of these infants required ad- mission to the NICU. Among 249 infants born to mothers ‘with class Al diabetes, the following diagnoses were made: ring Y chromosome (n=1), cleft palate (n=2), ileal atresia (n=), diaphragmatic hernia (n=1), duodenal atresia ( ‘gastroschisis (n=1), hydrocephalus (n=1), myelomenin- xgocele (n=1), hydronephrosis (n=2), hypoplastic kidneys (n=1), and Sturge-Parke-Weber syndrome (n=1). One pa- tient with hypoplastic left ventricle and one with congen- ital hydrocephalus were born to mothers with diabetes class ‘A2, One hundred seventy-cight infants were born to moth- ‘ers classified in the groups B through D-R. Ofthese, 13 (7%) presented with congenital malformations: achondropl- sia (n=1), microcephaly (n=1), racheoesophageal atresia and fistula (n=1), duodenal atresia (n=1), cleft palate (n=1), transposition ofthe great vessels (n=2), double outlet right ventricle (n=2), and ventricular septal defect (n=2). INTRAUTERINE FETAL GROWTH ‘Onchundred ninety-two (36%) ofthe530infantswereLGA, 327 (62%) were AGA, and only 11 (2%) were SGA (Table 1), Distribution according to maternal diabetic lass Pen icy 0, ns Castaic No tao "canta mors among 76 nts wth estaional ag of 3 week oss (ovematr) and 54a with gestanalageo 4 wees oy more. ROS Indeates esata ass syndrome ICU, reoat nen cae ani tion demonstrated that infants of mothers with class Al dia- betes had the lowest (259%) and those born to mothers with class C diabetes had the highest (62%) representation ofLGA, ‘The frequency of SGA infants was essentially equal among, the classes, Only 1 of 62 infants born to women with pre- eclampsia wasSGA. There were 190 LGA infants for whom the ponderal index was calculated. Of these, 155 (62%) were considered tobe proportionate and 35 (18%) were consid- creddisproportionately large Simnilarcalculations weremade for323 AGA infants. Three hundred seven (05%) were pro- portionate and 16 (5%) were disproportionately large, yet AGA. Thedilferencein the incidence of disproportionately large infantsbetween these 2 groups of patients was stais- ticaly significant (P<.01). The incidence of polycythemia, hypocalcemia, hyperbilirubinemia, and hypoglycemiaaind the number of NICU admissions among proportionateand disproportionate LGA infants was similar. “Macrosomia (birth weight =4000 g) occurred among 74 (1496) of 530 infants, and of this group, 42 (57%) were delivered by cesarean section. (Table 3) Morbidity in these Infants included 21 cases of hypoglycemia, 3 of polyeythe- mia, I of hypocalcemia, and 12 of hyperbilirubinemis. 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